Triethylamine → {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

HRID 1617366Notes

Reaction equation

HRID 1617366 reaction equation
Cl.Cl.Cl.[NH:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:13][C:12]([CH2:36][C:37]#[N:38])([N:14]3[CH:18]=[C:17]([C:19]4[C:20]5[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:21]=5[N:22]=[CH:23][N:24]=4)[CH:16]=[CH:15]3)[CH2:11]2)[CH2:6][CH2:5]1.[F:39][C:40]1[C:48]([C:49]([F:52])([F:51])[F:50])=[N:47][CH:46]=[CH:45][C:41]=1[C:42](O)=[O:43].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[F:39][C:40]1[C:48]([C:49]([F:52])([F:50])[F:51])=[N:47][CH:46]=[CH:45][C:41]=1[C:42]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:11][C:12]([CH2:36][C:37]#[N:38])([N:14]3[CH:18]=[C:17]([C:19]4[C:20]5[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[C:21]=5[N:22]=[CH:23][N:24]=4)[CH:16]=[CH:15]3)[CH2:13]2)[CH2:6][CH2:5]1)=[O:43]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 265964893-Fluoro-2-(trifluoromethyl)isonicotinic acidHCID 67391288{1-piperidin-4-yl-3-[3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride

Product 1

HCID 67391977{1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of {1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride (1.22 g, 2.03 mmol), 3-fluoro-2-(trifluoromethyl)isonicotinic acid (460 mg, 2.2 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.07 g, 2.42 mmol) and triethylamine (2.0 mL, 14 mmol) in DMF (20.0 mL) was stirred at room temperature overnight. LS-MS showed the reaction was complete. EtOAc (60 mL) and saturated NaHCO3 aqueous solution (60 mL) were added to the reaction mixture. After stirring at room temperature for 10 minutes, the organic phase was separated and the aqueous layer was extracted with EtOAc three times. The combined extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. Purification by flash chromatography provided {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile as a white powder.

Workup

  1. stirringAfter stirring at room temperature for 10 minutes
  2. customthe organic phase was separated
  3. extractionthe aqueous layer was extracted with EtOAc three times
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customPurification by flash chromatography

Sources & evidence

ORD record
ord-4673dcccf4ce48d789ef093ec9fd50f3
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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